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SARS-CoV-2 protease inhibitor + booster Pregnancy: Women of childbearing potential should avoid becoming pregnant during treatment, as there are only limited human data to inform the drug-associated risk of adverse developmental outcomes. Ritonavir may reduce the efficacy of combined hormonal contraceptives: patients using combined hormonal contraceptives should be advised to use an effective alternative contraceptive method or an additional barrier method during treatment and until after one complete menstrual cycle after stopping treatment. Pregnancy: there are limited data in pregnant women; use during pregnancy only if the potential benefits outweigh the potential risks for mother and foetus. Animal data with nirmatrelvir showed developmental toxicity in the rabbit (lower foetal body weights) but not in the rat, with no effect on foetal morphology or embryo-foetal viability at any dose tested; a large number of pregnancies exposed to ritonavir (6100 live births, 2800 exposed in the first trimester, largely at lower pharmacokinetic-enhancer doses similar to that used here) indicate no increase in the rate of birth defects. Breast-feeding: nirmatrelvir and ritonavir are excreted in breast milk in small amounts (milk to plasma AUC ratio 0.26 and 0.07 respectively; estimated daily infant dose 1.8% and 0.2% of the maternal dose), but there are no data on effects on the breast-fed infant or on milk production and a risk cannot be excluded - breast-feeding should be discontinued during treatment and for 48 hours after the last dose. Fertility: there are no human data on the effect on fertility; nirmatrelvir produced no effects on fertility in rats. The SPC's fertility paragraph is cut off at the source-fetch limit part-way through the ritonavir fertility statement.

Nirmatrelvir with ritonavir

Brand names: Paxlovid

An oral fixed combination antiviral (marketed as Paxlovid) for treating mild-to-moderate COVID-19 in non-hospitalised adults at increased risk of progressing to severe disease.

Adult dose

Dose: Treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk for progression to severe COVID-19: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), all taken together.
Route: Oral. The tablets should be swallowed whole and not chewed, broken or crushed. May be taken with or without food.
Frequency: Twice daily, every 12 hours, for 5 days. Give as soon as possible after a positive result of direct SARS-CoV-2 viral testing and within 5 days of onset of symptoms, even if baseline COVID-19 symptoms are mild.
Nirmatrelvir must be co-administered with ritonavir. Failure to correctly co-administer nirmatrelvir with ritonavir will result in plasma concentrations of nirmatrelvir that are insufficient to achieve the desired therapeutic effect. The SPC states this single fixed recommended dosage and does not print a separate maximum dose, so none is given here; the reduced regimens in moderate and severe renal impairment are set out under renal adjustment. Missed dose: take it as soon as possible if within 8 hours of the scheduled time, then resume the normal dosing schedule; if more than 8 hours have elapsed, do not take the missed dose and resume the normal schedule. If a patient requires hospitalisation for severe or critical COVID-19 after starting treatment, the full 5-day course should be completed at the discretion of the healthcare provider. Patients receiving a ritonavir- or cobicistat-containing regimen for HIV or HCV need no dosage adjustment and should continue that treatment; the dose remains 300 mg/100 mg twice daily for 5 days. A full review of concomitant medicines is essential before and during treatment: this is a strong CYP3A inhibitor and severe, life-threatening and fatal adverse reactions due to drug interactions have been reported. Safety and efficacy in patients younger than 18 years have not been established, so no paediatric dose is published.

Dose adjustments

Renal

No dosage adjustment is needed in mild renal impairment (eGFR 60 to under 90 mL/min). Moderate renal impairment (eGFR 30 to under 60 mL/min), days 1-5: 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet) twice daily. Severe renal impairment (eGFR under 30 mL/min) including those requiring haemodialysis: day 1 - 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) once; days 2-5 - 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet) once daily. Administer at approximately the same time each day for 5 days; on days of haemodialysis give the dose after haemodialysis. The daily dose pack supplied may contain more nirmatrelvir and ritonavir tablets than a renally impaired patient needs, so the patient must be alerted explicitly to the reduced number of tablets, and the remaining tablets disposed of in accordance with local requirements.

Hepatic

No dosage adjustment is needed for mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. Contraindicated in severe (Child-Pugh Class C) hepatic impairment - no pharmacokinetic or safety data are available.

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via the eMC — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • History of clinically significant hypersensitivity to the active substances (nirmatrelvir/ritonavir) or to any of the excipients listed in section 6.1
  • Severe hepatic impairment
  • Medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening reactions
  • Medicinal products that are potent CYP3A inducers, where significantly reduced plasma nirmatrelvir/ritonavir concentrations may be associated with loss of virologic response and possible resistance
  • Named contraindicated medicines in the SPC's Table 2 include: alfuzosin; ranolazine; neratinib; venetoclax; the antiarrhythmics amiodarone, bepridil, dronedarone, encainide, flecainide, propafenone and quinidine; fusidic acid; colchicine; astemizole and terfenadine; lurasidone, pimozide and quetiapine; silodosin; eplerenone and ivabradine
  • WARNING - INCOMPLETE LIST: the SPC's contraindicated-medicines table was cut off at the source-fetch limit part-way through the cardiovascular agents, and the SPC itself states that the medicinal products listed in its Tables 2 and 3 are a guide and not a comprehensive list. A full medication review against the current SPC and an interaction checker is essential before prescribing.

Side effects

  • Dysgeusia - the most common adverse reaction (5.9% with nirmatrelvir/ritonavir versus 0.4% with placebo)
  • Diarrhoea (2.9% versus 1.9% with placebo)
  • Nervous system disorders - common: dysgeusia, headache
  • Gastrointestinal disorders - common: diarrhoea, nausea; uncommon: vomiting, abdominal pain
  • Immune system disorders - uncommon: hypersensitivity; rare: anaphylaxis
  • Vascular disorders - uncommon: hypertension
  • Skin and subcutaneous tissue disorders - rare: toxic epidermal necrolysis, Stevens-Johnson syndrome
  • General disorders - rare: malaise
  • Anaphylaxis, hypersensitivity, hypertension, nausea, vomiting, abdominal pain, toxic epidermal necrolysis, Stevens-Johnson syndrome and malaise were identified post-marketing
  • The safety profile in participants with severe renal impairment, including those requiring haemodialysis, was consistent with that observed in the placebo-controlled trials

Monitoring

  • Concomitant medicines - review all concomitant medicinal products before and during treatment and monitor the patient for adverse reactions associated with those medicines; severe, life-threatening and fatal adverse reactions due to drug interactions have been reported. The risk of interactions during the 5-day course should be weighed against the risk of not receiving treatment.
  • Calcineurin inhibitors and mTOR inhibitors - consultation of a multidisciplinary group (for example physicians, specialists in immunosuppressive therapy and/or clinical pharmacology) is required, with close and regular monitoring of immunosuppressant blood concentrations and dose adjustment of the immunosuppressant in accordance with the latest guidelines.
  • Hypersensitivity - if signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue treatment and initiate appropriate medication and/or supportive care.
  • Liver - hepatic transaminase elevations, clinical hepatitis and jaundice have occurred in patients receiving ritonavir; exercise caution in patients with pre-existing liver disease, liver enzyme abnormalities or hepatitis.
  • HIV - because nirmatrelvir is co-administered with ritonavir, there may be a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection.

Clinical monograph

How it works

Nirmatrelvir inhibits the SARS-CoV-2 main protease (Mpro/3CL protease) to block viral polyprotein processing, while low-dose ritonavir acts purely as a pharmacokinetic booster by inhibiting CYP3A4 to maintain nirmatrelvir concentrations.

Prescribing in practice

  • The ritonavir component is a potent CYP3A4 inhibitor and causes numerous serious drug interactions — screen every co-medication (including statins, certain anticoagulants, antiarrhythmics, calcineurin inhibitors and sedatives) before prescribing and consult an interactions resource.
  • Must be started as early as possible and within a short defined window from symptom onset to be effective; review the SPC for renal dose adjustment as it is contraindicated in severe renal impairment.
  • Treatment course is short and time-limited; counsel on the possibility of symptom rebound after completion.

Monitoring

No routine laboratory monitoring is required for the short course, but renal and hepatic function should be checked at baseline and interacting drugs reviewed throughout.

Counselling the patient

  • Take both tablets together and complete the full short course even if you feel better.
  • Tell us about every medicine, supplement and herbal product you take, as some must be paused or avoided.
  • Some people notice symptoms briefly return after finishing — contact us if you become significantly more unwell.

Evidence & guidelines

The EPIC-HR trial demonstrated reduced risk of COVID-19-related hospitalisation or death in high-risk unvaccinated adults treated early.

Reference: UK COVID-19 therapeutic alerts; Liverpool DDI; SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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